Rzeszotarski et al., Eur. Pat. Appl. No. 0 251 126 published on Jan. 7, 1988, discloses 1,7-substituted heptyne-2-ones. The compounds of that invention can be prepared by reaction of an appropriate dithiane and ketone followed by removal of a dithiane protective group. See, the examples thereof for their preparation, and also, Example V for another preparation involving propargylation and Mannich condensation.
Rzeszotarski et al., U.S. patent application Ser. No. 07/155,110 filed on Feb. 11, 1988, discloses 1,7-substituted heptyn-2-ones and methods for their manufacture. These heptyn-2-ones can be prepared according to the practice of that invention by a variety of synthetic routes. One of these sequences involves Mannich condensation of pent-4-yn-1-ol with formaldehyde and the appropriate amine followed by sequential oxidation of the alcohol to an aldehyde, conversion of the aldehyde to a dithiane, condensation of the dithiane with an appropriate aryl ketone and lastly dithiane deprotection to the 1,7-substituted hept-5-yn-2-one. Another method involves addition of lithium acetylide to the aryl ketone, oxidation of the resulting acetylide to a methyl ketone which is sequentially propargylated to give an acetylenic derivative which is subjected to appropriate Mannich condensation. Alternatively, the methyl ketone can be alkylated with 1,4-dibromo-2-butyne to give a bromo derivative that can be alkylated to provide the product. In another route, the aryl ketone can be condensed with 1-(diethoxyphosphinyl)-1-trimetylsilyloxy ethane to give a methyl ketone that is propargylated and aminomethylated to give the product. Another sequence begins with an appropriate disubstituted glycolic acid which is converted to the methyl ketone that is transformed to product via the aforementioned propargylation, Mannich condensation sequence. According to another method, a 1-dialkoxyphosphinyl-1-trialkylsilyloxyethane having one to four carbons in one each of the alkyl and alkoxy groups is condensed with a ketone of the formula R'C(.dbd.O)R in which R has the meaning set forth in the general formula (IV) as described hereinafter, and R' is a phenyl or para-fluorophenyl group; the resulting 1,1-disubstituted-1-trialkylsilyloxy-2-propanone is propargylated followed by Mannich reaction of the product with formaldehyde and ammonia or an appropriate amine, which have the formula HNR" in which R" has the meanings set forth in the general formula (IV) as described hereinafter, and the silyl protecting group is thereafter removed. Yet another route for synthesizing the compounds involves ethynylation of a ketone to give a 1,1-disubsituted-1-hydroxypropyne which is oxidized to the corresponding 1,1-disubstituted-1-hydroxy propanone, which was alkylated with 1,4-dibromobutyne to yield 1,1-disubstituted-1-hydroxy-7-bromohept-5-yn-2-one, which is aminated to give the final compound.
Hansen et al., J. Am. Chem. Soc., 100, 2244 (1978), reports on nickel-catalyzed conjugate addition of organoaluminum acetylides to alpha, beta-enones.
Bruhn et al., Tetrahedron Lett., 235 (1976), reports on synthesis and properties of 16-hydroxy analogs of PGE2.
Sinclair et al., J. Am. Chem. Soc., 99, 954 (1977), reports on conjugate addition of B-1-alkynyl-9-borabicyclo[3.3.1]nonanes to alpha, beta-unsaturated ketones, a convenient synthesis of gamma, delta-acetylenic ketones.
Corey et al., J. Am. Chem. Soc., 96, 5581 (1974), reports on a nucleophilic ethynyl group equivalent and its use in conjugate addition to alpha, beta-enones.
Hoff et al., Rec. Trav. Chim., 87, 1179 (1968), reports on some conversions of allenyl ethers.
Keana et al., J. Org. Chem., 47, 347 (1982), reports on synthesis of diamagnetic structural analogues of representative doxyl, prolyl, piperidine, and pyrroline nitroxide spin labels. At page 348, a vinyl ketone (16) was reported to have resulted from a hydrolysis reaction.
Brandsma, "Preparative Acetylenic Chemistry, 2nd Ed.," Elsevier, 259 (1988), reports on methyl propargyl ether from propargyl alcohol, dimethyl sulfate and sodium hydroxide.
Hoff et al., Rec. Trav. Chim., 87, 916 (1968), reports on preparation, metallation and alkylation of allenyl ethers, to include methods related to reactions of allenes with butyllithium to prepare lithiated allenyl ethers.
Verkruijsse et al., Rec. Trav. Chim., 100, 244 (1981), reports on base-catalyzed isomerization of 2-propynylamines, synthesis of (dialkylamino)allenes, and preparation of 2-propynylamines.
What is lacking and what is needed in the art are solutions to problems presented. In particular, yields and purities of 1,7-substituted heptyn-2-ones would desirably be improved. Furthermore, improvements therein might find more widespread application in more generalized fields.